[en] In search for new anticancer agents, we have evaluated the antiinvasive and antimigrative properties of recently developed synthetic coumarin derivatives among which two compounds revealed important activity: 3-chlorophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate and 3-bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate, Both drugs were able to inhibit cell invasion markedly in a Boyden chamber assay, the bromo derivative being more potent than the reference matrix metalloprotease (MMP) inhibitor GI 129471. In vivo, tumour growth was reduced when nude mice grafted with HT 1080 or MDA-MB231 cells were treated i.p. 3 days week(-1) with the bromo coumarin derivative. These effects were not associated with the inhibition of urokinase, plasmin, MMP-2 or MMP-9. The mechanism of action of the drugs remains to be elucidated. However, these two coumarin derivatives may serve as new lead compounds of an original class of antitumour agents.
Foidart, Jean-Michel ; Université de Liège - ULiège > Département des sciences cliniques > Gynécologie - Obstétrique
Reboud-Ravaux, M.
Noël, Agnès ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie cellulaire et moléculaire appliquée à l'homme
Pirotte, Bernard ; Université de Liège - ULiège > Chimie pharmaceutique
Language :
English
Title :
3-Bromophenyl 6-acetoxymethyl-2-oxo-2H-1-benzopyran-3-carboxylate inhibits cancer cell invasion in vitro and tumour growth in vivo
Andreasen PA, Kjoller L, Christensen L, Duffy MJ (1997) The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer 72: 1-22
Attia MA, Weiss DW (1966) Immunology of spontaneous mammary carcinomas in mice. V. Acquired tumor resistance and enhancement in strain A mice infected with mammary tumor virus. Cancer Res 26(8): 1787-1800
Bender ML, Begue-Canton ML, Blakeley RL, Brubacher LJ, Feder J, Gunter CR, Kezdy FJ, Killheffer JVJ, Marshall TH, Miller CG, Roeske RW, Stoops JK (1966) The determination of the concentration of hydrolytic enzyme solutions: alpha-chymotrypsin, trypsin, papain, elastase, subtilisin and acetylcholinesterase. J Am Chem Soc 88: 5890-8913
Blacher S, Devy L, Burbridge M-F, Roland G, Tucker G, Noël A, Foidart JM (2001) Improved quantification of angiogenesis in the rat aortic ring assay. Angiogenesis 4(2): 133-142
Chase TJ, Shaw E (1970) Titration of trypsin, plasmin, and thrombin with p-nitrophenyl p′-guanidinobenzoate HCl. Methods Enzymol 19: 20-27
Coussens LM, Fingleton B, Matrisian LM (2002) Matrix metalloproteinase inhibitors and cancer: trials and tribulations. Science 295(5564): 2387-2392
Crescimano C, Foidart JM, Noël A, Polette M, Maquoi E, Birembaut Ph, Baramoua E, Kaufmann P, Castelluci M (1996) Cloning of choriocarcinoma cells shows that invasion correlates with the expression and activation of gelatinase A. Exp Cell Res 227: 240-251
Doucet C, Pochet L, Thierry N, Pirotte B, Delarge J, Reboud-Ravaux M (1999) 6-Substitued-2-oxo-2H-1-benzopyran-3-carboxylic acid as a core structure for specific inhibitors of human leukocyte elastase. J Med Chem 42: 4161-4171
Egeblad M, Werb Z (2002) New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer 2(3): 161-174
Frankenne F, Noël A, Bajou K, Sounni NE, Goffin F, Masson V, Munaut C, Remacle A, Foidart JM (1999) Molecular interactions involving urokinase plasminogen activator (uPA), its receptor (uPAR) and its inhibitor, plasminogen activator inhibitor-1 (PAI-1), as new targets for tumour therapy. Emerging Ther Targets 3(3): 1-13
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1): 57-70
Hooper JD, Clements JA, Quigley JP, Antalis TM (2001) Type II transmembrane serine proteases. Insights into an emerging class of cell surface proteolytic enzymes. J Biol Chem 276: 857-860
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(259): 680-685
Liotta LA (1986) Tumor invasion and metastases - role of the extracellular matrix: Rhoads Memorial Award lecture. Cancer Res 46(1): 1-7
Maquoi E, Munaut C, Colige A, Lambert C, Frankenne F, Noël A, Grams F, Krell HW, Foidart JM (1999) Paradoxical stimulation of matrix metalloproteinase-9 expression in HT1080 cells by a broad-spectrum hydroxamate-based matrix metalloproteinase inhibitor. Ann NY Acad Sci 30(878): 744-764
Masson V, Devy L, Grignet-Debrus C, Berndt S, Bajou K, Blacher S, Roland G, Chang Y, Fong F, Carmeliet P, Foidart JM, Noël A (2002) Mouse aortic ring assay: a new approach of the molecular genetics of angiogenesis. Biol Proced Online 4(1): 24-31
Noël A, Bajou K, Masson V, Frankenne F, Rakic JM, Lambert V, Carmeliet P, Foidart JM (1999) Regulation of cancer invasion and vascularization by plasminogen activator inhibitor-1. Fibrinolysis Proteolysis 13(6): 220-225
Noël A, Callé A, Emonard P, Nusgens BV, Simar L, Foidart J, Lapière C, Foidart JM (1991) Invasion of reconstituted basement membrane matrix is not correlated to the malignant metastatic cell phenotype. Cancer Res 51: 405-414
Noël A, Simon N, kleinman HK, Raus J, Foidart JM (1992) Basement membrane components (matrigel) promote human breast adenocarcinoma MCF7 cells tumorigenicity and provide an in vivo model to assess cell responsiveness to estrogen. Biochem Pharmacol 43: 1263-1267
Pochet L, Doucet C, Dive G, Wouters J, Masereel B, Reboud-Ravaux M, Pirotte B (2000) Coumarinic derivatives as mechanism-based inhibitors of α-chymotrypsin and human leukocyte elastase. Bioorg Med Chem 8: 1489-1501
Pochet L, Doucet C, Schynts M, Thierry N, Boggetto N, Pirotte B, Jiang KY, Masereel B, de Tullio P, Delarge J, Reboud-Ravaux M (1996) Esters and amides of 6-(chloromethyl)-2-oxo-2H-1-benzopyran-3-carboxylic acid as inhibitors of α-chymotrypsin: significance of the 'aromatic' nature of the novel ester-type coumarin for strong inhibitory activity. J Med Chem 39(13): 2579-2585
Powers JC, Gupton BF (1977) Reaction of serine proteases with aza-amino acid and aza-peptide derivatives. Methods Enzymol 46: 208-216
Reboud-Ravaux M, Desvages G (1984) Inactivation of human high- and low-molecular-weight urokinases. Analysis of their active site. Biochim Biophys Acta 791(3): 333-341
Reboud-Ravaux M, Desvages G, Chapeville F (1982) Irreversible inhibition and peptide mapping of urinary plasminogen activator urokinase. FEBS Lett 140(1): 58-62
Schmitt M, Wilhelm O, Reuning U, Krüger A, Harbeck N, Lengyel E, Graeff H, Gänsbacher B, Kessler H, Bürgle M, Stürzebecher J, Sperl S, Magdolen V (2000) The urokinase plasminogen activator system as a novel target for tumour therapy. Fibrinolysis Proteolysis 14(2/3): 114-132
Stetler-Stevenson WG, Liotta LA, Kleiner Jr DE (1993) Extracellular matrix 6: role of matrix metalloproteinases in tumor invasion and metastasis. FASEB J 7(15): 1434-1441
Takeuchi T, Harris JL, Huang W, Yan KW, Coughlin SR, Craik CS (2000) Cellular localization of membrane-type serine protease 1 and identification of protease-activated receptor-2 and single-chain urokinase-type plasminogen activator as substrates. J Biol Chem 275(34): 26333-26342
Wheeler DJ, Parveen S, Pollock K, Williams RJ (1998) Inhibition of sCD23 and immunoglobulin E release from human B cells by a metalloproteinase inhibitor, GI 129471. Immunology 95(1): 105-110
Workman P, Twentyman P, Balkwill F, Balmain A, Chaplin D, Double J, Embleton J, Newell D, Raymond R, Stables J, Stephens T, Wallace J (1998) United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) guidelines for the welfare of animals in experimental neoplasia (2 edn). Br J Cancer 77(1): 1-10
Zetter BR (1998) Angiogenesis and tumor metastasis. Annu Rev Med 49: 407-424